Approximately 1.3 million cases of cancer were diagnosed in North America in 2001. Over 50% of these have the potential to metastasize to bone [14]. Each year, over one hundred thousand bone metastases are identified. Post-mortem autopsy results from patients with primary cancer indicate that 60% of spines examined had metastatic lesions. An estimated twenty to forty thousand cases of metastatic breast cancer lesions alone occur in the spine each year [1,2]. Metastatic lesions to the spine result in intractable back pain, loss of bowel and bladder function, paresis and paralysis. The lesions can affect singular or multiple vertebral bodies.
In the ambulatory patient the mainstay of treatment is radiation therapy, while surgery is reserved for those experiencing collapse or neurological compromise. Unfortunately radiation therapy provides only limited relief from pain, does not provide stability to the spine and adversely affects the soft tissue such that the morbidity and mortality of surgical intervention is increased threefold [3,4,5]. Results of radiation therapy for the treatment of spinal metastases have shown that only one third have complete relief of their back pain [15]. Radiation therapy is limited by the number of times it can be administered as it affects the integrity of the soft tissues and can induce radiation myelopathy. As the longevity of patients with spinal metastases increases (average survival 2 years with breast cancer, mean 1 year survival of 78%) [16] so does the likelihood of lesion recurrence and the necessity for spinal surgery. Recurrence with radiation therapy is estimated to be 33% [1,17]. Spinal surgery for patients with spinal metastases carries a 30-40% risk of morbidity and a 7-16% risk of mortality.
Photodynamic therapy (PDT) can directly target lesions. PDT ablates tissue with a non-thermal specific wavelength of light delivered to the targeted tissue. A photosensitizing compound is administered prior to the light. The light activates the compound to a chemically excited state, the energy of which is then transferred to molecular oxygen producing reactive oxygen-derived species that are toxic to the surrounding tissue [8,18] [19,20]. There are reports that the drug is preferentially taken up and retained in tumor tissue compared to normal tissue [21,22] making the treatment somewhat specific. This therapy has been used in lung [9,10], intraperitoneal [11] and prostate cancer [12].
There are several photosensitizing compounds now available with minimal systemic side effect profiles. Benzoporphyrin derivative monoacid ring A (BPD-MA) is a photosensitizer that can be used to either target the neo-vasculature or produce intracellular cytotoxic effects based on the drug-light interval [6,7,23,24,25,26]. The vascular targets are primarily affected if the drug light interval is short (15 minutes or less) while the intracellular effects are seen in tissue if the drug light interval is long (3 hours) [6,24]. There are several reports of its use in soft tissue tumors in the murine model [20,23,25,27] as well as of its use in an orthotopic chondrosarcoma [6] and fibrosarcoma tumor models [24,26]. Results from these studies showed a significant effect at both the 15 minute and 3 hour drug light interval was achieved with 33% of the lesions being completely ablated at 4 weeks post treatment. The greatest effect was seen with the shorter interval demonstrating the potency of BPD-MA to affect the neo-vasculature.
To date, there have not been any published reports of the use of this therapy in bone or in the spine. To date, there have not been any published reports of PDT use in an in vivo metastatic breast cancer model affecting bone. To date, there have not been any published reports of the pharmacokinetics of BPD-MA for bone. There is a paucity of literature on the optical properties of bone.
Takeuchi et al., 1997 [28], reported on the optical properties of cancellous and cortical bone in comparison to muscle, fat and saline. Cortical bone has a high attenuation to light while cancellous bone does not.